Sokol L, Prchal J T
Department of Medicine, University of Alabama at Birmingham, USA.
Cas Lek Cesk. 1995 Oct 4;134(19):625-9.
Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of insulin receptor (INSR) are causative for rare syndromes of insulin resistance and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin receptor (EPOR) mutations are causative for rare primary familial and congenital polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR 1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant hyperthermia (MH) and central core disease (CCD). All these disorders represent group of receptor diseases. The amplification of GCT trinucleotide repeats in myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy (DM) and represents a new class of human gene mutations: trinucleotide repeat mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL. Interestingly adeno-associated virus (AAV), currently widely used as vector for gene therapy has unique capability of specific integration into human chromosome 19q.
19号染色体短小，但基因相对密度比其他染色体高。越来越多与各种人类疾病发病机制相关的蛋白质编码基因已被定位到19号染色体上。低密度脂蛋白受体（LDL-R）的突变导致最常见的孟德尔遗传性疾病之一——家族性高胆固醇血症。胰岛素受体（INSR）的突变是胰岛素抵抗罕见综合征和一些非胰岛素依赖型糖尿病（NIDDM）的病因。促红细胞生成素受体（EPOR）突变是罕见的原发性家族性和先天性红细胞增多症（PFCP）的病因。人类基因组中最大的基因之一RYR 1（兰尼碱受体基因）（大小超过240 kb）的缺陷是恶性高热（MH）和中央轴空病（CCD）的主要病因。所有这些疾病都属于受体疾病组。强直性肌营养不良蛋白激酶（DMPK）基因中GCT三核苷酸重复序列的扩增是强直性肌营养不良（DM）的病因，代表了一类新的人类基因突变：三核苷酸重复突变。载脂蛋白E（APOE）基因座在晚发性家族性阿尔茨海默病的发病机制中起作用。编码两种螺旋-环-螺旋（HLH）转录蛋白的EA2基因易位并与PBXI或肝白血病因子（HLF）融合，导致急性淋巴细胞白血病（ALL）亚组发生白血病。有趣的是，目前广泛用作基因治疗载体的腺相关病毒（AAV）具有特异性整合到人类19号染色体长臂（19q）的独特能力。
